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Updated: Sep 18, 2025
Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice
Published on: May 4, 2015
Ivermectin's neuroprotective effects decrease with prolonged use after cerebral ischemia/reperfusion
Sevda Rezaei1, Shabnam Babataheri1, Hamid Soraya2
1Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
Abstract:
Ivermectin (IVM), the recipient of the 2015 Nobel Prize, is an FDA-approved drug for a variety of parasitic diseases in animals and humans. However, the implications of this compound on neurological disorders remain inadequately elucidated. Recently, our research team has elucidated the neuroprotective properties of ivermectin administered in three doses following cerebral ischemia/reperfusion (IR). The objective of the current investigation is to ascertain whether ivermectin sustains its neuroprotective properties through prolonged administration in models of cerebral IR in rats, as well as to evaluate its impact on the formation of neutrophil extracellular traps (NETs). A rat model of transient global cerebral IR was induced by occluding both carotid arteries for 20 min. Ivermectin (2 mg/kg/day) was administered intraperitoneally one hour after the induction of cerebral ischemia for 7 consecutive days at 24-hour intervals. Then, the effects of ivermectin on brain infarct size, blood cell profile, bleeding time, memory and learning, balance and motor coordination, myeloperoxidase enzyme activity, and H3cit protein levels were investigated. The finding showed that the administration of ivermectin for 7 days did not improve memory and learning, blood parameters, or cerebral infarct size. However, it caused a 25.4% reduction in citrullinated histone protein level, decreased myeloperoxidase activity (P = 0.017), and improved balance and motor coordination (P = 0.017 and P = 0.024). In conclusion, our findings indicate that prolonged administration of ivermectin may diminish its neuroprotective effects and its effects can differ depending on the drug regimen.
Insights
Prolonged administration of ivermectin (IVM) did not improve cognitive function or infarct size after stroke in rats. However, it reduced markers of inflammation and improved motor coordination, suggesting varied effects based on drug regimen.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Ivermectin (IVM) is an FDA-approved antiparasitic drug with potential neuroprotective properties.
- Previous studies indicated neuroprotection with short-term ivermectin administration post-cerebral ischemia/reperfusion (IR).
- The effects of prolonged ivermectin administration on neurological disorders, particularly cerebral IR and neutrophil extracellular traps (NETs), require further investigation.
Purpose of the Study:
- To determine if prolonged ivermectin administration maintains neuroprotective effects in a rat model of cerebral IR.
- To evaluate the impact of sustained ivermectin treatment on NET formation and related inflammatory markers.
- To assess ivermectin's effects on cognitive function, motor skills, and infarct size following cerebral IR.
Main Methods:
- A transient global cerebral IR model was induced in rats by occluding carotid arteries.
- Ivermectin (2 mg/kg/day) was administered intraperitoneally for 7 consecutive days, starting 1 hour post-ischemia.
- Evaluated outcomes included brain infarct size, blood parameters, memory, motor coordination, myeloperoxidase activity, and citrullinated histone H3 (H3cit) levels.
Main Results:
- Seven-day ivermectin administration did not improve memory, learning, blood parameters, or cerebral infarct size.
- A significant reduction (25.4%) in citrullinated histone H3 protein levels was observed.
- Myeloperoxidase activity decreased significantly (P=0.017), and balance and motor coordination improved (P=0.017, P=0.024).
Conclusions:
- Prolonged ivermectin administration may alter or diminish its neuroprotective effects compared to shorter regimens.
- Sustained ivermectin treatment impacts inflammatory markers and motor function, but not cognitive recovery or infarct size in this model.
- The therapeutic efficacy of ivermectin in neurological disorders may be dependent on the specific drug administration schedule and duration.
